Funds are requested for a 15 Tesla ultra high-resolution Fourier transform ion cyclotron resonance (FT- ICR) mass spectrometer to support 21 NIH-funded research projects at the University of Wisconsin (UW)-Madison. This requested instrument has unprecedented analytical power and versatility, ultra high-resolution and high sensitivity, and a variety of tandem mass spectrometry (MS/MS) capabilities for top-down proteomics and metabolomics studies. The unique features of the requested ultra high-resolution FT-ICR mass spectrometer would differentiate it from other mass spectrometers currently in use on the UW- Madison campus. This requested high-end mass spectrometer will be used to carry out basic, translational, and clinical research dedicated to understanding the basis for human health and disease, identifying potential molecular targets for the treatment of disease, and developing high-throughput assays for early diagnosis and prevention of diseases. The research will have a direct impact on a number of human health issues, such as cardiovascular disease, cancer, neurodevelopmental disorders, and viral infection. The requested instrument will be housed in the Human Proteomics Program (HPP) Mass Spectrometry (MS) Core Facility as shared equipment accessible to all UW Users. It will be utilized for training Users on MS-related projects with a special focus on top-down proteomics and metabolomics. The new instrument will provide much-needed state-of-the-art research infrastructure for the 11 basic science and 13 clinical Departments in UW. It will also be available for external Users for their high-resolution and high accuracy MS needs. The UW School of Medicine & Public Health (SMPH) is committed to establishing a first-rate MS facility that is complementary to other mass spectrometry facilities on campus. Matching funds will be provided to support the service contract and staff salary to ensure the successful operation and maintenance of this high end instrument. Dedicated space is available to house this new instrument. The HPP MS core facility, initially established in 2006 by the funds from UW SMPH, is operated by highly qualified staff and is currently serving more than 30 research labs across the UW campus and other academic institutions. Specifically, the HPP MS core facility offers a unique top-down proteomics capability to proteomics researchers. Moreover, the HPP MS Facility is operated in a highly user friendly environment. The HPP MS facility staff, led by Dr. Ge, an expert in FT-ICR and top-down MS, has extensive experience in operating and maintaining FT-ICR instrument. Hence, the HPP MS core facility is ideally positioned to exploit the capabilities of cutting-edge top-down FT-ICR MS for biomedical research. The requested 15T ultra high-resolution FT-ICR will provide unique and essential advanced MS capabilities to meet the urgent needs and challenges of many NIH-funded research projects at UW-Madison.